Torque sensitive sanitary diaphragm valves for use in the pharmaceutical industry and methods related thereto

ABSTRACT

This invention relates to pressure torque sanitary diaphragm valves and methods of using torque sensitive sanitary valves in the production of chemical and biological therapeutics to obtain procedural reproducibility in the production pharmaceutical compounds and intermediates related thereto.

FIELD OF THE INVENTION

This invention relates to pressure torque sanitary diaphragm valves andmethods of using torque sensitive sanitary valves in the production ofchemical and biological therapeutics to obtain proceduralreproducibility in the production pharmaceutical compounds andintermediates related thereto.

BACKGROUND OF THE INVENTION

Pharmaceutical products are significant portion of the national economy,and the process used by pharmaceutical companies to produce theseproducts are regulated by the Food and Drug Administration (FDA). TheDivision of Manufacturing and Product Quality requires GoodManufacturing Practice for the production of human use pharmaceuticals.The FDA regulates the production of pharmaceuticals to ensure that themethods utilized produce a pharmaceutical products are of high qualityand provides Certificates of Pharmaceutical Products to firms thatlegally market drug products.

The production of medicines requires the utilization of mechanicalmethods for manipulation of solid and fluid chemical compounds andmixtures. More specifically the transfer of chemical and biologicalsolutions and mixtures will require the use of equipment that is able tobe thoroughly cleaned and sanitized preventing contamination of insubsequent use. Improperly sanitizing equipment can result incontamination of the products produced in subsequent batches addingconsiderable cost. Steam sterilization is currently a preferred methodof sanitizing equipment used in pharmaceutical manufacturing. Valves areof significant importance as equipment used in pharmaceuticalmanufacturing because they are often used to control the flow andtransfer of chemicals including biologics and biological organisms.

Because in ordinary valves closing the valve causes the valve's stem toprotrude into the flow area and opening the valve causes the stem toretract into the stem's housing area, often chemicals that are in theflow area may get trapped between the middle of the stem and the stem'shousing area. The trapped chemicals are often difficult to remove duringa sanitizing process allowing the trapped chemicals to be reintroducedinto the flow area when the valve is subsequently used.

To overcome sanitation problems in using ordinary valves for theproduction of pharmaceutical and biological products, sanitary diaphragmvalves have been developed. In a sanitary diaphragm valves a diaphragmis introduced between the stem and the flow area. The diaphragm is aflexible material that has a chemical contact side and a stem contactside. During rotation of the handle, the stem contacts the diaphragmpushing the diaphragm's chemical contact side into the flow area forminga seal with the surrounding flow housing area obstructing the flow ofsolutions. Sanitary diaphragm valves are widely used in thepharmaceutical and biotechnology industries for the processing oftherapeutic and biological medicines. These valves have the feature thatthe diaphragm's chemical contact surface can be steam sterilized. Thisis typically done in advance of fluid processing in order to reduce thechance that unwanted chemicals are introduced into the drug product.

One major problems of using diaphragms in current valves is that thediaphragm can warp and/or become irregular and may not seal properlywhen the operator manually closes the valve because the diaphragms areexposed to the extreme conditions of the steam sterilization proceduremultiple times and because over exertion of pressure from the stem dueto over rotating the handle. Because current valve diaphragm designsutilizes a stem with a fixed operation range, obtaining a proper closureseal depends on proper placement of the diaphragm to prevent leakagefrom the valve due to improper sealing.

Pharmaceutical and biotechnology companies recognize the warping andsealing problems of current diaphragm valves for some time and many haveinstituted preventative maintenance programs that require regularreplacement of diaphragms. Unfortunately, these measures have notprovided to be a satisfactory solution because it is not easy to predictwhen diaphragm warping will occur and typically the problem is detectedtoo late—generally after a biological contamination that resulted from abreach to the sterile barrier. In addition, the success of diaphragmreplacement can vary from operator to operator and therefore may requirelabor intensive leak testing and re-replacement in order to assure noleaks are present for a even new diaphragm.

BRIEF SUMMARY OF THE INVENTION

This invention relates to torque sensitive sanitary diaphragm valves andmethods of using torque sensitive sanitary valves in the production ofchemical and biological therapeutics to obtain proceduralreproducibility in the production pharmaceutical compounds andintermediates related thereto. More specifically, this invention relatesto the insertion of pressure sensitive slipping mechanisms in sanitarydiaphragm valves between the valve's handle and the valve's stem,between the attachment areas of the valve's handle and the valve's stemor in between the attachment areas of the valve's handle and the valve'sstem housing area.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

FIG. 1A. In this invention the housing contains a flow housing area (1)and a stem housing area (3). The flow housing area (1) is a location ona pipe, tubing, or other structure utilized to facilitate the flow ofsolutions between two areas where there is a desired to prevent the flowof the solutions. The stem housing area (3) is a hollow structure, suchas a tube, with a first opening attached to the flow housing area and asecond opening threaded for the stem. The stem (4) has a top, a middle,and a bottom. The top of the stem is attached to the slipping mechanism(5). The slipping mechanism (5) is attached to the handle (6). Themiddle of the stem is counter-threaded for the threaded stem housing'sattachment area. The bottom of the stem is shaped to mate with the shapeof the flow housing area. The diaphragm (2) is a flexible material thathas a chemical contact side and a stem contact side. The diaphragm (2)is located in the first opening of the stem housing between the stem andthe flow housing area.

FIG. 1B. Closing the valve is accomplished by rotation of the handle (6)causing the threaded and counter-threaded stem housing's stem attachmentarea and stem's stem housing attachment area respectively to move thestem (4) vertically down the stem housing area (3) until the bottom ofthe stem moves through the first opening of the stem housing into theflow housing area (1). During rotation of the handle, the stem (4)contacts the diaphragm (2) pushing the diaphragm's chemical contact sideinto the flow housing area (1) ultimately forming a seal with thesurrounding flow housing area as the bottom of the stem mates with theflow housing area obstructing the flow of solutions. As diaphragm (2)compresses, the stem will begin to exert pressure on the handlerequiring an increase the amount of torque necessary to continuerotating the handle. When a pre-set torque is exerted on the handle, theslipping mechanism (5) will allow the handle to rotate but will notallow the threaded stem housing and counter-threaded stem to furtherengage preventing the stem from apply additional pressure on thediaphragm.

FIG. 2. The stem housing area (3) is a hollow structure, such as a tube,with a first opening attached to the flow housing area, a secondopening, and a handle attachment area threaded for attachment of thehandle. The stem (4) has a top, a middle, and a bottom. The top of thestem is attached to the handle (6). The stem (4) is attached to thehandle (6) in a manner allowing the handle to rotate freely or pivotwithout rotation of the stem. The middle of the stem is enclosed in thestem housing area. The bottom of the stem is shaped to mate with theshape of the flow housing area (1). The handle (6) contains acounter-threaded stem housing attachment area for attachment to thethreaded stem housing's handle attachment area. The diaphragm (2) is aflexible material that has a chemical contact side and a stem contactside. The diaphragm (2) is located in the first opening of the stemhousing (3) between the stem (4) and the flow housing area (1). Theslipping mechanism (5) is located either between the stem housing andthe stem housing's threaded handle attachment area or between the handleand the handle's counter-threaded stem housing attachment area.

FIG. 3. The stem (4) has a top, a middle, and a bottom. The middle andtop of the stem are threaded as an area for attachment of the handle.The bottom of the stem is shaped to mate with the shape of the flowhousing area (1). The middle and bottom of the stem is enclosed in thestem housing area (3), and the top of the stem protrudes out through thesecond stem housing opening. The handle (6) contains a stem housingattachment area and a counter-threaded stem attachment area. The handle(6) is attached to the stem housing (3) in a manner allowing the handleto rotate freely or pivot without rotation of the stem housing. Thediaphragm (2) is a flexible material that has a chemical contact sideand a stem contact side. The diaphragm (2) is located in the firstopening of the stem housing between the stem and the flow housing area.The slipping mechanism (5) is located between the handle (6) and thehandle's counter-threaded stem attachment area.

DETAILED DESCRIPTION OF THE INVENTION

The critical feature sanitary diaphragm valve is the pressure obtainwhen mating the stem bottom, the diaphragm, and the flow area. If thevalve diaphragm warps and a valve stem no longer provides proper sealingforce when the operator places the valve in the fully closed position,then the valve will leak until it is disassembled and the diaphragmmanually adjusted. By expanding the valve stem travel range of operationand modifying the valve handle to “slip” when a pre-set torque isreached, a reproducible seal pressure is achieved resulting in superiorcost effective manufacturing capabilities.

Pressure sensitive sanitary diaphragm valves contain five majorcomponents: a housing, a stem, a handle, a diaphragm, and a slippingmechanism.

In one example of this invention the housing contains a flow housingarea and a stem housing area. The flow housing area is a location on apipe, tubing, or other structure utilized to facilitate the flow ofsolutions between two areas where there is a desired to prevent the flowof the solutions. The stem housing area is a hollow structure, such as atube, with a first opening attached to the flow housing area and asecond opening threaded for the stem. The stem has a top, a middle, anda bottom. The top of the stem is attached to a slipping mechanism. Theslipping mechanism is attach to the handle. The middle of the stem iscounter-threaded for the stem housing's second opening. The bottom ofthe stem is shaped to mate with the shape of the flow housing area. Thediaphragm is a flexible material that has a chemical contact side and astem contact side. The diaphragm is located in the first opening of thestem housing between the stem and the flow housing area. The slippingmechanism is located between the handle and the stem.

Closing the valve is accomplished by rotation of the handle causing thethreaded and counter-threaded stem housing's stem attachment area andstem's stem housing attachment area respectively to move the stemvertically down the stem housing area until the bottom of the stem movesthrough the first opening of the stem housing into the flow housingarea. During rotation of the handle, the stem contacts the diaphragmpushing the diaphragm's chemical contact side into the flow housing areaultimately forming a seal with the surrounding flow housing area as thebottom of the stem mates with the flow housing area obstructing the flowof solutions. As diaphragm compresses, the stem will begin to exertpressure on the handle requiring an increase the amount of torquenecessary to continue rotating the handle. When a pre-set torque isexerted on the handle, the slipping mechanism will allow the handle torotate but will not allow the threaded stem housing and counter-threadedstem to further engage preventing the stem from apply additionalpressure on the diaphragm.

Opening the valve is accomplished by counter-rotation of the handlecausing the threaded and counter-threaded stem housing's stem attachmentarea and stem's stem housing attachment area respectively to move thestem vertically up the stem housing area and the bottom of the stem outof the flow housing area back through the first opening of the stemhousing into the hollow area of the stem housing.

The slipping mechanism can be created in variety of ways well-know tothose skilled in the art. For example, the embodiments of this inventioninclude a slipping mechanism that contains a top and a bottom thatengage each other. The top attached to the handle is affixed with agear, such as a sprocket. The bottom attached to the stem contains acylinder with flexible strips of metal placed to reside within thenotches of the gear and affixed to the inner cylinder. When the torqueis sufficient the strips of metal will bend allowing the gear to rotate;thus, creating a “slip” in the handle.

In another example of this invention the housing contains a flow housingarea and a stem housing area. The flow housing area is a location on apipe, tubing, or other structure utilized to facilitate the flow ofsolutions between two areas where there is a desired to prevent the flowof the solutions. The stem housing area is a hollow structure, such as atube, with a first opening attached to the flow housing area, a secondopening, and a handle attachment area threaded for attachment of thehandle. The stem has a top, a middle, and a bottom. The top of the stemis attached to the handle. The stem is attached to the handle in amanner allowing the handle to rotate freely or pivot without rotation ofthe stem. The middle of the stem is enclosed in the stem housing area.The bottom of the stem is shaped to mate with the shape of the flowhousing area. The handle contains a counter-threaded stem housingattachment area for attachment to the threaded stem housing's handleattachment area. The diaphragm is a flexible material that has achemical contact side and a stem contact side. The diaphragm is locatedin the first opening of the stem housing between the stem and the flowhousing area. The slipping mechanism is located either between the stemhousing and the stem housing's threaded handle attachment area orbetween the handle and the handle's counter-threaded stem housingattachment area.

Closing the valve is accomplished by rotation of the handle causing thethreaded and counter-threaded stem housing's handle attachment area andhandle's stem housing attachment area respectively to move the stemvertically down the stem housing area until the bottom of the stem movesthrough the first opening of the stem housing into the flow housing areacausing obstruction of the flow of solutions through the flow housingarea. During rotation of the handle, the stem contacts the diaphragmpushing the diaphragm's chemical contact side into the flow housing areaultimately forming a seal with the surrounding flow housing area as thebottom of the stem mates with the flow housing area obstructing the flowof solutions. As diaphragm compresses, the stem will begin to exertpressure on the handle requiring an increase the amount of torquenecessary to continue rotating the handle. When a pre-set torque isexerted on the handle, the slipping mechanism will allow the handle torotate but will not allow the threaded stem housing and counter-threadedhandle to further engage preventing the stem from apply additionalpressure on the diaphragm.

Opening the valve is accomplished by counter-rotation of the handlecausing the threaded and counter-threaded stem housing's handleattachment area and handle's stem housing attachment area respectivelyto move the stem vertically up the stem housing area and the bottom ofthe stem out of the flow housing area back through the first opening ofthe stem housing into the hollow area of the stem housing.

In another embodiment of this invention the housing contains a flowhousing area and a stem housing area. The stem housing area is a hollowstructure, such as a tube, with a first opening attached to the flowhousing area, a second opening, and a handle attachment area. The stemhas a top, a middle, and a bottom. The middle and top of the stem arethreaded as an area for attachment of the handle. The bottom of the stemis shaped to mate with the shape of the flow housing area. The middleand bottom of the stem is enclosed in the stem housing area, and the topof the stem protrudes out through the second stem housing opening. Thehandle contains a stem housing attachment area and a counter-threadedstem attachment area. The handle is attached to the stem housing in amanner allowing the handle to rotate freely or pivot without rotation ofthe stem housing. The diaphragm is a flexible material that has achemical contact side and a stem contact side. The diaphragm is locatedin the first opening of the stem housing between the stem and the flowhousing area. The slipping mechanism is located either between the stemand the stem's threaded handle attachment area or between the handle andthe handle's counter-threaded stem attachment area. The closing andopening of the valve is accomplished as described in the previousembodiments.

Another embodiment of this invention is a pharmaceutical valve for usewith biological and chemical transfer equipment having a housing with aflowing housing area having a shape for the transfer of a solutionthrough the flow housing area, and a stem housing area having a firstopening attached to the flow housing area and a second opening threadedfor vertical motion within the stem housing area, the pharmaceuticalvalve comprising: a stem with a top, a middle counter-threaded for thestem housing's second opening, and a bottom shaped to mate with theshape of the flow housing area; a handle; a diaphragm with a chemicalcontact side and a stem contact side located in the first opening of thestem housing between the stem and the flow housing area; and a slippingmechanism located between the handle and the stem.

Another embodiment of this invention is a pharmaceutical valve for usewith biological and chemical transfer equipment having a housing with aflowing housing area having a shape for the transfer of a solutionthrough the flow housing area, and a stem housing area having a firstopening attached to the flow housing area and a second opening threadedfor vertical motion within the stem housing area, the pharmaceuticalvalve comprising: a stem with a top, a middle counter-threaded for thestem housing's second opening, and a bottom shaped to mate with theshape of the flow housing area; a handle counter-threaded for attachmentto the stem housing attachment area and affixed to the stem allowing thehandle to pivot without rotation of the stem; a diaphragm with achemical contact side and a stem contact side located in the firstopening of the stem housing between the stem and the flow housing area;and a slipping mechanism located either between the stem housing and thestem housing's threaded handle attachment area or between the handle andthe handle's counter-threaded stem housing attachment area.

Another embodiment of this invention is a pharmaceutical valve for usewith biological and chemical transfer equipment having a housing with aflowing housing area having a shape for the transfer of a solutionthrough the flow housing area, and a stem housing area having a firstopening attached to the flow housing area and a second opening having ahandle attachment area for vertical motion within the stem housing area,the pharmaceutical valve comprising: a stem with a top and a middle boththreaded as an area for attachment of the handle, and a bottom shaped tomate with the shape of the flow housing area; a handle counter-threadedfor attachment to the threaded stem's handle attachment area andattached to the stem housing allowing the handle to pivot withoutrotation of the stem housing; a diaphragm with a chemical contact sideand a stem contact side located in the first opening of the stem housingbetween the stem and the flow housing area; and a slipping mechanismlocated between the handle and the stem.

Another aspect of this invention are methods of preventing the flow offluids in equipment making biological or chemical therapeutics usingtorque sensitive sanitary diaphragm valves according to the embodimentsof this disclosure.

1. A torque sensitive sanitary diaphragm valve comprising: (a) a housinghaving a flow housing area with a shape for the transfer of solutionthrough the flow housing area and a stem housing area with a firstopening attached to the flow housing area and a second opening threaded;(b) a stem with a top, a middle counter-threaded for the stem housing'ssecond opening, and a bottom shaped to mate with the shape of the flowhousing area; (c) a handle; (d) a diaphragm with a chemical contact sideand a stem contact side located in the first opening of the stem housingbetween the stem and the flow housing area; and (e) a slipping mechanismlocated between the handle and the stem.